The central goal of this research is a better understanding of the pathophysiology of stroke. The major effort is directed toward developing and implementing better methods to enable study of important physiological mechanisms, in conjunction with highly sophisticated mathematical modeling and computer simulation. The major projects include perfection of the 133 Xenon inhalation rCBF method, introducing some original new concepts and application of these in a variety of pathologic states and during focal activation; perfection of a variety of electrochemical and electrophysiological measurements of local flow and metabolism for study of experimental ischemia and hypoxic in animals; analysis of the membrane events leading to irreversible hypoxic depolarization in the Aplysia neurone correlating this with similar biophysical measurements in a vertebrate axon; study of blood and tissue factors which impede microflow; and implementation of a non-invasive measurement of regional oxygen metabolism in acute stroke utilizing infra red light.